Congenital Hyperinsulinism Center Zeroes in on New Drug

CHOP researchers are investigating a new drug that could revolutionize treatment for congenital hyperinsulinism (HI) by managing glucose levels in even the most severe forms of the disease — without surgery.

HI is a rare disease in which the pancreas makes too much of the hormone insulin, causing blood glucose to plummet. Depriving the brain of the sugars it needs to function can damage it quickly.

CHOP’s Congenital Hyperinsulinism Center is the only facility with a multidisciplinary team dedicated to caring for these children and doing research to improve the management of their condition, according Diva De León, MD, the center’s director.

Currently, about half of HI cases can be treated with medication or cured by surgically removing portions of the pancreas. For the other half, the only option is to remove the pancreas entirely or most of it. Consequently, many of these children will need a feeding tube to control blood sugar until they are 5 to 7 years old, and almost all will develop diabetes.

A decade of research has helped Dr. De León to understand how insulin-secreting pancreatic cells work. She zeroed in on an investigational drug called exendin-(9-39), which showed success in decreasing insulin production in mice. Exendin-(9-39) is a modified form of exendin-4, a synthesized version of a protein derived from Gila monster saliva that is currently used to treat diabetes.

The results of Dr. De León’s clinical trial, the first using this drug in humans, were published in the journal Diabetes. They showed that exendin-(9-39) successfully increased fasting blood glucose and inhibited insulin secretion in nine patients.

This study, funded by grants from the National Institutes of Health and donations from the Lester and Liesel Baker Foundation and the Clifford and Katherine Goldsmith Foundation, provides proof of concept that will allow for larger studies in the future and hopefully U.S. Food and Drug Administration approval of the medication. The center is preparing an expanded clinical study for 2014.